Molecular docking study based on pharmacophore modeling for novel PhosphodiesteraseIV ınhibitors

dc.contributor.authorAkdoğan, Ebru Demet
dc.contributor.authorAviyente, Viktorya
dc.contributor.authorAkten, Ebru Demet
dc.date.accessioned2019-06-27T08:04:03Z
dc.date.available2019-06-27T08:04:03Z
dc.date.issued2012
dc.departmentFakülteler, Mühendislik ve Doğa Bilimleri Fakültesi, Biyoinformatik ve Genetik Bölümüen_US
dc.description.abstractIn this study pharmacophore modelling was carried out for novel PhosphodiesteraseIV (PDEIV) inhibitors. A pharmacophore-based virtual screening which resulted in 1959 hit compounds was performed with six chemical databases. The pharmacophore screening was proven to be successful in discriminating active and inactive inhibitors using a set of compounds with known activity obtained from ChEMBL database. Furthermore the Lipinskis rule of five was applied for physicochemical filtering of the hit molecules and this yielded 1840 compounds. Three docking software tools AutoDock 4.0 AutoDock Vina and Gold v5.1 were used for the docking process. All 1840 compounds and the known selective inhibitor rolipram were docked into the active site of the target protein. A total of 234 compounds with all three scoring values higher than those of rolipram were determined with the three docking tools. The interaction maps of 14 potent inhibitors complexed with PDEIV B and D isoforms have been analyzed and seven key residues (Asn 395 Gln 443 Tyr 233 Ile 410 Phe 446 Asp 392 Thr 407) were found to interact with more than 80?% of the potent inhibitors. For each one of the 234 hit compounds using the bound conformation with the highest AutoDock score the interacting residues were determined. 117 out of 234 compounds are found to interact with at least five of the seven key residues and these were selected for further evaluation. The conformation with the highest AutoDock score for each 117 compounds were rescored using the DSX scoring function. This yielded a total of 101 compounds with better score values than the natural ligand rolipram. For ADME/TOX calculations the FAF-Drugs2 server was used and 32 out of 101 compounds were found to be non-toxic.en_US]
dc.identifier.citation4
dc.identifier.doi10.1002/minf.201100141en_US
dc.identifier.endpage471
dc.identifier.issn1868-1743en_US
dc.identifier.issn1868-1743
dc.identifier.pmid27477465en_US
dc.identifier.scopus2-s2.0-84864198471en_US
dc.identifier.scopusqualityN/A
dc.identifier.startpage459en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12469/884
dc.identifier.urihttps://doi.org/10.1002/minf.201100141
dc.identifier.volume31en_US
dc.identifier.wosWOS:000306478200006en_US
dc.identifier.wosqualityQ2
dc.institutionauthorAkten, Ebru Demeten_US
dc.language.isoenen_US
dc.publisherWiley-VCH Verlag GmbHen_US
dc.relation.journalMolecular Informaticsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectMolecular dockingen_US
dc.subjectPharmacophore modelingen_US
dc.subjectPhosphodiesteraseIV inhibitorsen_US
dc.titleMolecular docking study based on pharmacophore modeling for novel PhosphodiesteraseIV ınhibitorsen_US
dc.typeArticleen_US
dspace.entity.typePublication
relation.isAuthorOfPublication558d2b8e-c713-49e0-9350-d354abb5cd69
relation.isAuthorOfPublication.latestForDiscovery558d2b8e-c713-49e0-9350-d354abb5cd69

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Molecular docking study based on pharmacophore modeling for novel PhosphodiesteraseIV ınhibitors.pdf
Size:
12.89 MB
Format:
Adobe Portable Document Format
Description: